Selective hydrolysis of dialkyl ethers of protocatechuic aldehyde



United States Patent 3,367,972 SELECTIVE HYDROLYSIS 0F DlALKYL ETHERS 0F PROTOCATECHUIC ALDEHYDE Wayne Benjamin Gitchcl, Rothschild, Edmunds Modrins Pogainis, Mosinec, and Eugene Wilhelm Schoetfel, Kronenwetter, Wis, assignors to Sterling Drug, Inc., New York, N.Y., a corporation of Delaware No Drawing. Filed Nov. 19, 1964, Ser. No. 412,302 Claims. (Cl. 260-600) ABSTRACT @F THE DESCLOSURE Alkyl vanillins, e.g., ethyl vanillin, are produced by selectively hydrolyzing a dialkyl ether of protocatechuic aldehyde with concentrated sulfuric acid, to a 4-monoether; re-alkylating to another dialkyl ether and selectively hydrolyzing that dialkyl ether under basic conditions at a temperature above 200 C. to a 3-rnono-ether.

This invention relates to chemical processes comprising the selective hydrolysis of alkyl aryl ethers, more particularly to processes comprising the selective hydrolysis of dialkyl ethers of protocatechuic aldehyde, and process'es utilizing this selective hydrolysis, including those for the production of ethylvanillin, i.e., bourbonal (3-ethoxy- 4-hydroxybenzaldehyde) The invention sought to be patented resides in the concept of converting vanillin to ethylvanillin, in the concept of converting veratric aldehyde to a 3-alkoXy-4-hydroxybenzaldehyde in which the alkoxy group has at least 2 carbon atoms by selectively hydrolyzing veratric aldehyde to isovanillin with concentrated mineral acid, alkylating the isovanillin to 3 alkoxy 4 methoxybenzaldehyde in which the alkoxy group is higher than methoxy and selectively hydrolyzing the 3-alkoxy-4-methoxy-benzaldehyde to 3-alkoxy-4-hydroxybenzaldehyde with an aqueous hydrolyzing agent at a pH above 7 under pressure at a temperature above 200 C., and in the concept of selectively hydrolyzing dialkyl ethers of protocatechuic aldehyde to produce by selection of hydrolyzing agents and hydrolysis conditions, either the 3- or 4-monoether in high yield.

Because of a better and stronger flavor, ethylvanillin now commands a higher price than vanillin, i.e., up to about 4 times the price of vanillin. Therefore, it is desirable commercially to have a process which can inexpensively convert vanillin to ethylvanillin.

A process for converting vanillin to ethylvanillin is disclosed in US. Patent 2,878,292. This process involves as its first step the hydrolysis of vanillin to protocatechuic aldehyde. However, as later disclosed by the same inventor in US. Patent 2,975,215, protocatechuic aldehyde production from vanillin in high yield is not readily achieved. Only by the use of specialized reagents and conditions is a good yield achieved, The thus-produced protocatechuic aldehyde can selectively be alkylated to ethyl vanillin in only 77 percent yield. The latter patent states higher yields can be obtained if the by-products are recycled. However, on a commercial scale the recycling of by-products containing substantial amounts of protocatechuic aldehyde is very difiicult, for one reason because of the ease with which this compound decomposes into cannizzaro-type products and polymerizes to black resins.

By the process of this invention, the use of the relatively labile protocatechuic aldehyde as an intermediate and specialized ether cleavage reagents is avoided by first alkylating the vanillin to veratric aldehyde and converting the veratric aldehyde to ethyl or other alkyl vanillin. If desired, the process can start with isovanillin, a compound "ice which up to now had little utility, thus eliminating the first of the selective ether cleavage steps.

In accordance with this invention, veratric aldehyde is selectively hydrolyzed in high yield to isovanillin with concentrated mineral acid. The thus-produced isovanillin is alkylated to S-ethoxyor other desired 3-alkoxy-4-methoxy-benzaldehyde, which is then selectively hydrolyzed under alkaline conditions at elevated temperature and pressure to the corresponding 3-alkoxy-4-hydroxy-benzaldehyde.

German Patent 622,966 discloses the conversion of isovanillin to ethylvanillin via the mixed. diether of protocatechuic aldehyde using glacial acetic acid and 48 percent HBr as the hydrolytic agent. However, these materials are unpleasant and relatively expensive hydrolytic agents compared With the alkaline hydrolytic agents of this invention and the selectivity is poor. Alkaline hydrolyzing agents have been used to remove the readily cleaved benzyl group from 3-methoxy-4-benzyloxybenzaldehyde. See US. Patents 487,204, 545,099 and 561,077. They have not been used to selectively cleave in high yield the 4-ethers of a 3,4-dialkyl diether of protocatechuic aldehyde.

Surprisingly, although the process involves two selective hydrolysis steps, higher over-all yields can be achieved than by a complete hydrolysis followed by monoalkylation or followed by dialkylation and the same type selective hydrolysis. Because veratric aldehyde can be prepared from sources other than vanillin, the process of this invention employs veratric aldehyde as starting material. However, in a preferred aspect vanillin is converted to ethylvanillin. Also, the novel selective hydrolysis steps developed for use in the conversion of veratric aldehyde to eth-yl vanillin have independent utility in the preparation of 3-monoand 4-mono-ethers of protocatechuic aldehyde, which monoethers are useful as intermediates in the production of a variety of chemical compounds.

The alkylation of a vanillin to veratric aldehyde is a Well-known reaction. Nearly quantitative yields can be obtained using a molar equivalent or more of dimethyl sulfate and about a molar equivalent of sodium hydroxide, potassium hydroxide, sodium methoxide or other agent capable of forming a basic metallic salt of the phenolic hydroxy group. Methyl iodide, methyl bromide or methyl chloride can also be used, if desired. See US. 3,007,968, 2,490,842 and 2,496,803; Org. Synthesis, Collective Volume II, page 619 (1943), John Wiley & Sons, Inc. Pub.

SELECTIVE ACIDIC HYDR OLYSIS The selective cleavage of veratric aldehyde and other 3,4-dialkox y-benzaldehydes to produce the corresponding 4-monoether can be achieved using acidic hydrolysis conditions, e.g., concentrated mineral acid.

Sulfuric acid is generally regarded as not a suitable agent for the cleavage of ether groups in labile compounds. See Burwell, Chemical Reviews, vol. 54, page 615 (1954). Moreover, other strong acids have been used to selectively remove the 4-ether of veratric aldehyde. See German Patent 622,966. It is therefore surprising this preferred acidic hydrolyzing agent selectively cleaves the 3- ether of veratric aldehyde to give very good yields of isovanillin, calculated on veratric aldehyde consumed, under the conditions employed. Although the conversion rate of veratric aldehyde to isovanillin is relatively low, i.e., in the order of up to 65 percent, yields calculated on the veratric aldehyde consumed, with recycling of the veratric aldehyde, is from 99 percent.

In this acidic hydrolysis step, a molar excess of mineral acid, preferably sulfuric acid, is ordinarily used, e.g., at least 3:1, calculated on the aldehyde, preferably 4:1 to 11:1 and more preferably about 5:1 to 10:1. Below a 3:1 ratio, yield of isovanillin drops. Above 11:1 ratio, there is no advantage in yield. The molar ratio of mineral acid to H O employed in the reaction is important and should beat least 2:1, e.g., from about 2:1 to 10:1, preferably about 2:1 to 8:1, most preferably about 4: 1. Thus, sulfuric acid of a concentration of about 92 to 98 percent, more preferably 94 to 96 percent, is used.

The preferred reaction temperature is about 60 to 105 0, preferably 70100 C., e.g., about 80 to 95 C, The optimum reaction time at any selected reaction conditions is determined by the products produced. If 10 percent or more protocatechuic aldehyde is obtained under the selected reaction conditions, lower temperatures should be used. If the yield of isovanillin is lower than optimum, longer reaction times and/ or temperatures can be employed. At 60 up to 24 hours may be required; at 70 about 26 hours is usually required; at 105, 30-90 minutes or less sufiices. At optimum temperature, about 1 to 3 hours is the optimum reaction time.

The ratio of isovanillin to vanillin produced varies from about 5:1 to 15:1 with the higher ratios generally being obtained at the lower hydrolysis temperatures. The optimum balance between yields and conversion rate is realized at about a 50 to 60 percent conversion.

The thus-produced isovanillin preferably can be isolated by diluting the reaction mass with water, preferably to a 30-50 percent H 50 concentration, extracting the organics from the aqueous mixture with solvent, extracting the products from the solvent extract with water at a pH above 9, and then lowering of the aqueous extract to a pH between 8 and 9, most preferably about 8.3 to selectively precipitate the isovanillin. The diluted acid can, if desired, be re-used by reconstituting with S0 or fuming sulfuric acid.

Any organic solvent system which is not miscible in the diluted acid and in which the isovanillin is soluble can be used as the extraction solvent. For example, a mixture of ethylene dichloride and chloroform or carbon tetrachloride, a mixture of 'butanol and a non-polar solvent, e.g., benzene, toluene or xylene, diethylether, bromobenzene, etc., can be used. A 30:70 to 10:90 by volume mixture works very well with butanol and toluene.

Alternatively, the reaction mixture can first be neutralized, e.g., with caustic, potash, lime, calcium carbonate, caustic soda, to a pH above 9, extracted with solvent and then the pH lowered to between 8 and 9 to precipitate the isovanillin.

This sulfuric acid selective hydrolysis is also well suited for the conversion of other 3,4-diethers of protocatechuic aldehyde in which the alkoxy groups are the same or different and are, e.g., methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, octoxy, nonoxy, and cycloalkoxy including cyclopentoxy and cyclohexoxy, preferably those containing 1-8 carbon atoms and those in which the 4- alkoxy group contains at least the number of carbon atoms of the 3-alkoxy group and desirably more, to produce the corresponding 4-monoether. Especially preferred are those in which the 3-ether is the 3-methyl ether. The process can also be used to produce 4-allyl and other alkenyl, 4-5- hydroxyethyl and other functionally substituted alkyl, 4- phenyl and other aryl 4-mono-ethers of protocatechuic aldehyde, which compounds are useful as intermediates in the production of diverse pharmaceutical and polymer chemicals and as plasticizers and antioxidants for plastic films. Examples of such starting compounds are 3-ethoxy-, 3-n-propoxy, 3-butoxy, 3-pentoXy-, 3-hexoxy-, 3-heptoxy, 3-octoxy-, 3-phenoxy-, and 3-cyclo-hexoXy-4-methoxybenzaldehyde, which can be prepared by the appropriate 3-alkylation of isovanillin, and the corresponding higher '4-alkyl homologues, e.g., 3-cyclohexoxy-4-ethoxy-benzaldehyde and 3,4-diethoxybenzaldehyde, which can be prepared by appropriate alkylation of a 3-alkoxy-4-hydroxybenzaldehyde or 3-hydroxy-4-alkoxy-benzaldehyde.

Other concentrated mineral acids, e.g., hydrochloric, hydrobromic, sulfurous or phosphoric and strong organic acids such as the sulfonic acids, e.g., p-toluene sulfonic acid, can be used under somewhat more strenuous reaction conditions. However, these other acids generally give lower yields of desired product and/or lower conversion rates.

Isovanillin and other 4-monoethers of .protocatechuic aldehyde alkylate in high yield to 3,4-diethers using the alkylating conditions described above. Ethyl chloride is an ideal alkylating agent although diethyl sulfate, ethyl iodide, ethyl bromide, etc., can also be used. For higher alkyl ethers of 28 carbon atoms, e.g., propyl, ispropyl, 'butyl, the corresponding alkyl chloride, bromide or iodide can be used. Alternatively, other known etherification techniques can be employed to produce the alkyl or, if desired, aryl, alkaryl, alkenyl, cycloalkyl, or cycloalkenyl ether. Conditions as vigorous as those described in US. 2,878,292 and even more so can be used. The product can be isolated in the same manner as veratric aldehyde.

SELECTIVE ALKALINE HYDROLYSIS The selective cleavage of 3-ethoxy-4-methoxy-benzaldehyde and other 3,4-dialkoxy-benzaldehydes to produce the corresponding 3-monoether can be achieved using alkaline hydrolysis conditions, e.g., at a pH of at least 9 and preferably11-14 at elevated temperatures.

The hydrolysis reaction is conducted at between about 200 and 325, preferably from 240-300 and most preferably from 250-275 C. The lower limit is determined by hydrolysis rate and the upper limit by loss of selectivity and decomposition of the products. Sufficient pressure is employed to prevent substantial volatilization of the water. About 5 to 50 p.s.i.g. above the steam pressure produced at the selected temperature suflices.

Any alkaline material or mixtures of alkaline materials which will provide an alkaline pH at the reaction temperature can be used in the hydrolysis, e.g., the alkalimetal hydroxides, preferably sodium or potassium hydroxide, the alkali-metal carbonates, preferably sodium carbonate, the alkali-metal carbonates, preferably sodium bicarbonate, the alkali-metal sulfites, lime, calcium carbonate, trisodium phosphate, etc. A reducing agent, e.g., one to two moles of sodium sulfite or sodium bisulfite per mole of aldehyde in the reaction mixture, increases yields. The alkali-metal hydroxides, carbonates and bicarbonates, alone or in mixture with an alkali-metal sulfite or bisulfite, are the preferred hydrolyzing agents.

The molar ratio of hydrolyzing agent to 3-alkoxy-4- methoxy-benzaldehyde has a significant effect upon the yield of protocatechuic aldehyde 3-mono-ether obtained. Desirably, no more than a 1:1 molar ratio of hydrolyzing agent to aldehyde is employed although ratios as high as 4:1 are operable. At a pH above 11, e.g,. using an alkalimetal hydroxide, from about 0.5 to 1.05 moles hydrolyzing agent to aldehyde is preferably employed.

The alkaline hydrolysis of a 3-alkoxy-4-methoxybenzaldehyde provides very high ratios of 3-mono-etherto 4-mono-ether. The pressure of the reducing agent maintains at a minimum the production of undesired byproducts.

The reaction product can be isolated by lowering the pH of the reaction mixture to less than 9, preferably about 8.3, and extraction with solvent, e.g., ethylene dichloride or one of the solvents described above for the isolation of the isovanillin. The solvent can then be removed by distillation and the 3-alkyl mono-ether of protocatechuic aldehyde purified, if desired, by fractional crystallization. A mixture of methanol and water is an excellent purification solvent for ethyl vanillin.

This alkaline selective hydrolysis is also useful for the conversion of 3,4-diethers of protocatechuic aldehyde in which the alkoxy groups are the same or different, e.g., methoxy, ethoxy, isopropoxy, n-butoxy, octoxy, nonoxy, and cycloalkoxy including cyclopentoxy and cyclohexoxy,

preferably those containing 1-8 carbon atoms and those in which the 3-alkoxy group contains at least the number of carbon atoms as the 4-alkoxy group, desirably more. Especially preferred are those in which the 4-ether is the methyl ether. It can also be used to produce 3-allyl and other alkenyl, 3-6-hydroxy and other functionally substituted alkyl, and 3-phenyl and other aryl monoethers of protocatechuic aldehyde, which compounds are useful as flavorings, odorants, oil antifoaming agents, plasticizers and antioxidants for plastic films, intermediates, e.g., by conversion of the aldehyde group to the corresponding acid esters which have preservative and disinfectant activity, and conversion to the hydrazones thereof which have herbicidal activity. Examples of such starting compounds are 3-ethoxy-, B-n-propoxy, 3-butoxy, 3-pentoxy-, 3-hexoxy-, 3-heptoXy-, 3-octoxy, 3-phenoxy-, and 3-cyclohexoXy-4-methoxy-benzaldehyde, which can be prepared by the appropriate 3-alkylation of isovanillin, and the corresponding higher 4-alkyl homologues, e.g., 3-cyc1ohexoxy- 4 ethoxy benzaldehyde and 3,4 diethoxybenzaldehyde, which can be prepared by appropriate alkylation of a 3-alkoxy-4-hydroxybenzaldehyde or 3-hydroxy-4-alkoxybenzal-dehyde.

The above described selective acid and alkaline hydrolysis reactions, in a preferred aspect, can be represented as follows:

OOH

wherein n and m are integers from 1 to 8 and, when the hydrolysis is acidic, m is equal to or greater than n and is preferably 1 and, when the hydrolysis is alkaline, n is equal to or greater than m and is preferably at least 2.

Example 17.-Selective hydrolysis of veratric aldehyde to isovarzillin TABLE I.ACID HYDROLYSIS OF VERATRIC ALDEHYDE Time (111111.)

Percent V.A. converted to Percent Yield sale. on

Veratric aldehyde. 2 Isovanillin. Vanillin. 4 Protoeateehuie aldehyde.

In Table II the results of further runs in which the H SO :H O and H SO :VA ratios were varied at various reaction times and temperatures.

TABLE II.*H2SO4 HYDROLYSIS OF VERATRIC ALDEHYDE (VA) TO ISOVANILLIN (IV) Percent Reaction Reaction Products, percent Percent Wt. Ratio H2O in Time Reaction Rat-i0 IV Yield ealcd. H 80 VA H2804 (mins) Temp. C.) IV Van. PCA VA unreto Van. on VA conaeted sumed Run 36 shows that at temperatures below 70 C., longer reaction times are needed to achieve good conversions. Between 60 and 70 C. about 18-24 hours are required. Run 35 illustrates the fact that at temperatures'above about 110 C. yield drops. Lower than about 70 C., low conversions are achieved at reaction times below about 18 hours. Run 37 shows the adverse elfect on conversion rate and yield of excessive water. Run 38 shows the adverse effect on conversion rate of H SO :VA weight ratios below about 1.75:1 (molar ratios below about 3:1).

Following the above procedure, 3-ethoxy-4-methoxy-, 3-octyloxy-4-methoxy, 3,4-diethoxy-, 3-ethoxy-4-propoxy, 3,4-dipropoxyand 3,4-dioctyloXy-protocatechuic aldehyde are selectively hydrolyzed, respectively, to A-methoxy-, 4-methoxy-, 4-ethoxy-, 4-propoxy-, 4-propoxy and 4-octyloxy-protocatechuic aldehyde.

Example 2.Alkalz'n e hydrolysis of 3-eth0xy-4-meth0xybenzaldehyde t ethylvanillin In the following runs, 17.8 g. (0.1 mole) of 3-ethoxy-4- methoxy-benzaldehyde, 300 cc. of 0.5 M aqueous Na SO and 100 cc. of 1.0 M NaOH were heated in an evacuated sealed nickel bomb in a 450 C. salt bath under the conditions shown in Table III.

TABLE V Time (sec) from Temp.,C.

beginning of Pressure,

heating Salt Bath Reaction p.s.i.g.

Mixture 120 395 225 610 180 384 279 1, 000 210 bath removed 290 1, 080 240 bath removed 298 1, 080 270 bath removed 296 1, 000

The reaction mixture was at a temperature at which reaction occurs at asubstantially rapid. rate (225 and. d above) for only about 2.5 of the 4.5 minutes during which the mixture was heated. This is equivalent to about 1.5 to 2 minutes holding time at 290298 C. in a continuous reactor.

Example 3.C0nversi0n 0f vanillin t0 ethylvanillin TABLE III.ALKALINE HYDROLYSIS OF 3-ETHOXY-4-METHOXY-BENZALDEHYDE Time (sec) Peak Percent EMB converted to- Percent Yield No. Temp, C. EMB and Heat-up At Temp. E.V. I.V. P.G.A. I.V. recycled) 1 3-ethoxy4-methoxy-benzaldehyde. 2 Ethylvanillin. 5 Isovanillln. 4 Protocatechuic aldehyde.

Following the above procedure, 3,4-diethoxy-, 3-propoXy-4-methoxy-, 3-propoxy-4-ethoxy-, 3,4-dipropoxy, 3- octyloxy-4-methoxyand 3,4-dioctyloxy-protocatechuic aldehyde are selectively hydrolyzed, respectively, to ethylvanillin, propylvanillin, propylvanillin, propylvanillin, octylvanillin and octylvanillin.

Table IV shows runs similar to those of Example 2 in which reactants at the indicated concentrations were reacted at various temperatures and times. Runs 8 to 16 were continuous runs in which the reactants were passed for the indicated times through a heated tubular reactor. Run 8 illustrates the adverse effect upon yield of molar ratios of NaOHzEMB in excess of about 1:1. Table V gives in more detail the reaction conditions employed in sodium hydroxide (34.9 percent by weight). The temperature rises to about 107 C. Regulate addition rate so as to maintain the reaction temperature at 107 C. during the additions. Time of addition is about 100 minutes. Ex-

tract the resulting veratric aldehyde oil with ethylene diover a 15 minute period to 5500 grams of 66 B. sulfuric acid at 83 C. The temperature rises to 92 C. Hold at 92 C. :1 for 120 minutes. Cool the acid solution to 15 C. and pour into 32 liters of water at 16. The temperature rises to C. Extract the diluted acid with ethylene Run 5, which was typical of those employed in Runs 1 55 dichloride and wash the extract with 3.5 M sodium hydroxide. Distill the solvent from the washed extract to TABLE IV.-ALKALINE HYDROLYSIS OF 3-ETHOXY-4-METHOXYBENZALDEHYDE (EMB) TO ETHYL VANILLI'N '(EV) McL/l M01./l. Mol./1. Total Temp Reaction Products ercent EMB Na SO; NaOH Reaction C.) p 1%???) Tune (m1n.) E.V. I.V. P.O.A. Gannizzaro Unreacted IV 0. 25 0. 375 0. 25 3. 25 260-70 69. 8 1. 5 0. 4 9.0 12.9 47-1 0. 25 0. 375 0. 25 3. 33 270- 77. 0 1. 8 0. 5 8. 5 5. 7 43. 1 0. 246 0. 375 0. 25 3. 0 270-75 80. 0 2. 0 0. 4 7. 1 3. 2 40:1 0. 25 0. 375 O. 25 3. 33 280- 78. 7 1. 9 6. 4 8. 2 3. 2 .41-1 0. 25 0. 375 0. 25 4. 5 290-298 81. 3 1. 9 2. 9 4. 9 1. 0 .41 Z 1 0. 25 0. 375 0.25 4. 5 290-298 78. 3 1. 7 2. 8 4. 3 1. 0 46 1 0.25 0.375 0.25 4. 83 290-296 80.6 2.0 2. 2 6.1 1. 7 .40 1 0. 249 0. 376 0.87 3. 85 255 63. 3 1. 4 0. 7 15. 2 0.3 451 0. 253 0. 371 0. 25 3. 85 254 72. 5 0. 7 0. 5 9. 4 5.9 1 0.253 0.371 0.25 2. 6 265 72.7 1.6 0. 5 6. 8 6. 9 45 1 0. 251 0. 373 0. 25 3. 75 275 81. 8 2. 0 0. 5 4. 2 0. 4 41 1 0.252 0.371 0.25 3.9 277 79. 5 2.1 0. 6 4. 2 0. 5 38 1 0. 255 0. 368 0. 25 4. 0 275 78. 7 1. 9 0. 6 4. 2 0. 3 41 z 1 0. 243 0. 380 0. 25 4.05 273 84. 3 2. 2 0. 6 2. 4 0.2 42 1 0.24 0.373 0. 24 3. 7 274 87. 2 2.5 0. 8 3.0 1. 0 35 1 0. 24 0. 373 0. 24 3. 8 275 88. 8 2. 3 0. 7 3. 6 0. 9 3921 Runs 8 through 16 are continuous reactor runs.

recover about 272 grams of unreacted veratric aldehyde. Lower the pH of the aqueous sodium hydroxide wash to 8.3 with 50 percent sulfuric acid. Wash the precipitate, filter and dry. 515 g. of isovanillin is obtained, a yield of 71 percent calculated on the veratric aldehyde which reacted.

Introduce 1000 grams of isovanillin, prepared according to the above procedure, into a mechanically agitated autoclave along with 645 grams ethyl chloride, 400 grams sodium hydroxide and 11,500 grams water. Heat the mixture with agitation for 30 minutes at 150 C. and 96 p.s.i.g. maximum pressure. Cool the reaction mixture, adjust to a pH of 3.7 With 50 percent sulfuric acid and extract with ethylene dichloride. Wash the extract with aqueous sodium hydroxide and remove the solvent by distillation. There is obtained about 850 grams of 3-ethoxy- 4-methoxy-benzaldehyde, a 77 percent yield.

Pump simultaneously a 0.24 mole/liter solution of 3- ethoxy-4-methoxy-benzaldehyde in 0.373 mole/liter sodium bisulfite and 1.25 mole/liter aqueous sodium hydroxide at equal rates into an oil jacketed tubular reactor so as to convert the bisulfite solution to a sodium sulfitesodium hydroxide solution. Maintain a jacket temperature of 275 C. and a residence time of 3.8 minutes. Extract the resulting alkaline reaction mixture with ethylene dichloride, treat with sulfur dioxide, and filter to remove small amounts of 3-ethoxy-4-methoxy benzyl alcohol and 3-ethoxy-4-methoxy benzoic acid. Acidify the purified bisulfite solution with sulfuric acid, boil, and extract with ethylene dichloride. Remove the solvent by distillation, leaving about 820 grams crude ethylvanillin per 1000 grams of 3-eth0xy-4-methoxy-benzaldehyde. Vacuum distill and crystallize from aqueous methanol to produce white crystalline pure ethylvanillin melting at 77-78 C.

Following the procedure of Example 3, a nearly quantitative conversion of vanillin to veratric aldehyde is achieved. About 60-65 percent conversion of the veratric aldehyde to isovanillin is achieved with a recycle of about 20-30 percent of the starting veratric aldehyde recovered from the reaction product, thus achieving a yield of about 87-95 percent in this step. The ethylation of the isovanillin is achieved at a conversion rate of 75-90 percent with about 8-10 percent of unreacted isovanillin being recycled to achieve about a 95 percent yield. In the final selective hydrolysis step, about an 80-90 percent conversion to ethylvanillin is achieved with a recycle of about -20 percent of the ethylvanillin to the recrystallization step to achieve about a 75-80 percent yield of pure crystalline ethylvanillin, an overall yield of pure ethylvanillin from vanillin of about 65 percent.

Following the above precedure, but substituting diethylsulfate or ethyl chloride for the dirnethyl sulfate, vanillin is converted to ethylvanillin with 3-meth0xy-4-eth0xy benzzaldehyde and 3,4-diethoxy-benzaldehyde as intermediates. By the use of appropriate alkylating agents, vanillin is converted to the 3-phenyl, 3-cyclohexyl, 3-propyl, 3- 21121, B-n-hexyl, and other 3-ethers of protocatechuic alde- What is claimed is:

1. A process for converting a 3-monoether of protocatechuic aldehyde to another 3-monoether which comprises the steps of (a) alkylating a 3-alkyl rnonoether of protocatechuic aldehyde containing from l-8 carbon atoms with an alkylating agent to produce the 3,4-diether of protocatechuic aldehyde in which the alkoxy groups each contain from 1-8 carbon atoms and the 4-alkoxy group contains at least the number of carbon atoms of the 3-alkoxy group,

(b) selectively hydrolyzing the resulting diether of protocatechuic aldehyde with 92-98 percent sulfuric acid in a molar ratio of sulfuric acid to said diether of at least 3:1 and at a temperature between about 60 and 110 C. to produce the 4-monoetl1er,

(c) alkylating the thus-produced 4-monoether with an alkylating agent to produce an alkyl diether of protocatechuic aldehyde in which the 3-alkoxy group contains l-8 carbon atoms and at least the number of carbon atoms as the 4-alkoxy group and differs from that of the starting 3-monoether, and

(d) hydrolyzing the thus-produced diether with an aqueous alkaline hydrolyzing agent at a pH of at least 11 under pressure at a temperature above 200 C. to produce the 3-monoether of protocatechuic aldehyde.

2. A process according to claim 1 wherein the hydrolyzing agent of step (d) is selected from the group consisting of alkali-metal hydroxides, alkali-metal carbonates and alkali-metal bicarbonates.

3. A process according to claim 1 wherein the hydrolysis mixture of step (d) comprises an alkali metal salt of a reducing acid.

4. A process according to claim 1 wherein in step (dl there is present about a molar equivalent of sodium hydroxide and at least a molar equivalent of sodium sulfite, each calculated on the aldehyde, and a reaction temperature between about 240-3 00 C. is employed.

5. A process according to claim 1 wherein the alkylating agent in step (a) is a methylating agent and in step (d) an ethylating agent.

6. A process for producing from veratric aldehyde an alkyl vanillin of the formula wherein n is an integer from 2 to 8 which comprises the steps of (a) selectively hydrolyzing veratric aldehyde with 92-98 percent sulfuric acid in a molar ratio of acid to veratric aldehyde of at least 3:1 and at a temperature between about and C. to produce isovanillin, (b) alkylating the thus-produced isovanillin with an alkylating agent to produce a diether of protocatechuic aldehyde of the formula wherein n has the value given above, and

(c) hydrolyzing the thus-produced diether under pressure at 240-300 C with an aqueous alkaline hydrolyzing agent selected from the group consisting of alkali-metal hydroxides, alkali-metal carbonates and alkali-metal bicarbonates.

7. A process for producing ethylvanillin from veratric aldehyde which comprises the steps of (a) selectively hydrolyzing the veratric aldehyde with 92-98 percent sulfuric acid at a temperature between about 80 and 95 C. to produce isovanillin,

(b) alkylating the isovanillin to 3-ethoxy-4-methoxybenzaldehyde, and

(c) selectively hydrolyzing the 3-ethoxy-4-methoxybenzaldehyde with about a molar equivalent of aqueous alkaline metal hydroxide, in the presence of at least a molar equivalent an alkali-metal salt of reducing acid, each calculated on the aldehyde, under pressure at a temperature between about 240-300 C.

8. A process for the selective hydrolysis of a 3,4-di- 75 alkyldiether of protocatechuic aldehyde in which each alkoxy group contains 1-8 carbon atoms and the 4-alkoxy group contains at least the number of carbon atoms of the '3alkoxy group, to produce the 4-monoether as the major product which comprises heating the diether with 92-98 percent sulfuric acid in a molar ratio of acid to said diether of at least 3:1 at a temperature between about 60 and 110 C.

9. A process according to claim 8 wherein the diether is veratric aldehyde.

10. A process according to claim 8 wherein the reaction temperature is between about 80 and 95 C.

11. A process for the selective hydrolysis of veratric aldehyde to produce isovanillin which comprises contacting veratric aldehyde with 9496 percent sulfuric acid, in an H SO IV61atI'lC aldehyde molar ratio of from 4:1 to 11:1 at a temperature between about 8095 C.

12. A process for the selective hydrolysis of a 3,4-dialkyl diether of protocatechuic aldehyde to produce the corresponding 3-monoether as the major product which comprises hydrolyzing the diether with an aqueous alkaline hydrolyzing agent at a pH of at least 11 under pressure at a temperature above 200 C.

13. A process according to claim 12 wherein the 4-alkyl group is methyl, and the 3-a1kyl group is ethyl.

14. A process according to claim 12 wherein the hydrolyzing agent is selected from the group consisting of alkali-metal hydroxides, alkali-metal carbonates and alkali-metal bicarbonates.

15. A process for the selective hydrolysis of 3-ethoxy- 4-methoxybenzaldehyde to ethylvanillin which comprises hydrolyzing the diether with about a molar equivalent of aqueous sodium hydroxide and at least a molar equivalent of sodium sulfite under pressure at a temperature between about 240 and 300 C.

BERNARD HELFIN, Primary Examiner. 

